Piaron forte

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT PIARON® FORTE (PIARON FORTE)

Composition:

Active ingredients: paracetamol, caffeine;

One tablet contains paracetamol 500 mg, caffeine 65 mg;

Excipients: citric acid anhydrous, sorbitol (E 420), dimethicone, aspartame (E 951), povidone, sodium bicarbonate, sodium carbonate anhydrous, sodium lauryl sulfate.

Pharmaceutical form. Effervescent tablets.

Main physicochemical properties: white or almost white tablets, round, with beveled edges, flat on both sides.

Pharmacotherapeutic group. Analgesics and antipyretics.

ATC code: N02BE51.

Pharmacological Properties

Pharmacodynamics. Paracetamol is an analgesic and antipyretic agent. Its effect is based on inhibition of prostaglandin synthesis in the central nervous system (CNS). Peripheral prostaglandin synthesis is only minimally affected, making paracetamol partially suitable for patients for whom inhibition of peripheral prostaglandins is undesirable (e.g., patients with a history of gastrointestinal bleeding).

Caffeine enhances analgesic efficacy through its stimulant effect on the CNS, which may counteract the depression often associated with pain.

Pharmacokinetics. Paracetamol and caffeine are rapidly and almost completely absorbed in the gastrointestinal tract. Paracetamol is uniformly distributed throughout all body fluids, with minimal plasma protein binding at therapeutic doses.

Paracetamol and caffeine are primarily metabolized in the liver and excreted in the urine as metabolites.

Clinical Characteristics

Indications. Moderate to severe pain (headache, migraine, musculoskeletal pain, muscle pain, dental pain, post-extraction pain and dental procedures, sore throat, menstrual pain), fever and post-vaccination pain, elevated body temperature.

Contraindications

• Hypersensitivity to paracetamol, caffeine, or any other component of the medicinal product.
• Cardiovascular disorders, including organic (marked increase in arterial pressure, severe atherosclerosis, severe hypertension, decompensated heart failure, acute myocardial infarction, paroxysmal tachycardia).
• Severe hepatic dysfunction (including congenital hyperbilirubinemia).
• Severe renal dysfunction.
• Gastrointestinal disorders (acute pancreatitis).
• Epilepsy.
• Increased excitability; sleep disturbances.
• Blood disorders (including severe anemia; leukopenia; glucose-6-phosphate dehydrogenase deficiency).
• Endocrine disorders (hyperthyroidism; severe forms of diabetes mellitus).
• Closed-angle glaucoma.
• Alcoholism.
• Elderly age (over 60 years).
• Phenylketonuria (see section "Special precautions").
• Concomitant use with:
  • monoamine oxidase inhibitors (MAOIs) and within 2 weeks after discontinuation of their use;
  • tricyclic antidepressants;
  • beta-blockers.

Interaction with other medicinal products and other types of interactions

The absorption rate of paracetamol may be increased when used with metoclopramide and domperidone, and decreased when used with cholestyramine. The anticoagulant effect of warfarin and other coumarins, with an increased risk of bleeding, may be enhanced due to prolonged regular use of paracetamol. Single doses do not show a significant effect.

Caution should be exercised when using paracetamol concomitantly with flucloxacillin, as such concomitant use has been associated with metabolic acidosis with a high anion gap due to pyroglutamic acidosis, especially in patients with risk factors (see section "Special precautions").

Barbiturates reduce the antipyretic effect of paracetamol. Anticonvulsants (particularly phenytoin, barbiturates, carbamazepine), which stimulate hepatic microsomal enzyme activity, may enhance the hepatotoxic effect of paracetamol due to increased conversion of the drug into hepatotoxic metabolites. Concomitant use of paracetamol with hepatotoxic agents increases the hepatotoxic effects of the drugs. Concurrent use of high doses of paracetamol with isoniazid increases the risk of developing hepatotoxic syndrome. Paracetamol reduces the efficacy of diuretics.

Do not use concomitantly with alcohol.

Concomitant use of caffeine with monoamine oxidase inhibitors (MAOIs) may cause a dangerous increase in blood pressure. Caffeine enhances the effect (improves bioavailability) of analgesic-antipyretic agents, potentiates the effects of xanthine derivatives, alpha- and beta-adrenergic agonists, and psychostimulants.

Cimetidine, hormonal contraceptives, and isoniazid enhance the action of caffeine.

Caffeine reduces the effect of opioid analgesics, anxiolytics, hypnotics, and sedatives; it acts as an antagonist of anesthetic agents and other drugs that depress the CNS, and as a competitive antagonist of adenosine and ATP (adenosine triphosphate) preparations. When used concomitantly with ergotamine, caffeine improves the gastrointestinal absorption of ergotamine; when used with thyroid-stimulating agents, it enhances the thyroid effect.

Caffeine may increase lithium excretion from the body. Therefore, concomitant use of the medicinal product with lithium preparations is not recommended.

Special precautions for use

The medicinal product contains paracetamol; therefore, it should not be used in combination with other medicinal products containing paracetamol, such as those used for fever reduction, pain relief, flu and cold symptoms, or insomnia. Concurrent use with other paracetamol-containing products may lead to overdose. Paracetamol overdose can cause liver failure, which may necessitate liver transplantation or result in fatal outcomes.

Cases of impaired liver function or liver failure have been reported in patients with reduced glutathione levels, for example, in severe malnutrition, anorexia, low body mass index, chronic alcoholism, or sepsis.

Cases of high anion gap metabolic acidosis due to 5-oxoproline (pyroglutamic acid) accumulation have been reported in patients with severe underlying conditions such as severe renal insufficiency and sepsis, or in patients with malnutrition or other sources of glutathione deficiency (e.g., chronic alcoholism), who have been receiving long-term therapeutic doses of paracetamol or a combination of paracetamol and flucloxacillin. In suspected cases of high anion gap metabolic acidosis caused by pyroglutamic acidosis, immediate discontinuation of paracetamol is recommended, along with careful monitoring. Measurement of 5-oxoproline levels in urine may be useful in identifying pyroglutamic acidosis as the underlying cause of high anion gap metabolic acidosis in patients with multiple risk factors.

Patients with reduced glutathione levels are at increased risk of developing metabolic acidosis when taking paracetamol. Symptoms of metabolic acidosis include deep, rapid, or labored breathing, nausea, vomiting, and loss of appetite. Immediate medical attention should be sought if these symptoms occur.

If symptoms persist, consult a physician.

During treatment with this medicinal product, excessive consumption of beverages containing caffeine (such as coffee, tea, and certain other drinks) is not recommended. This may lead to sleep disturbances, tremors, heart palpitations with chest discomfort, nervousness, and irritability.

In patients with liver or kidney disease, medical advice should be sought before using this product. Restrictions on use in such patients are primarily due to the presence of paracetamol. It should be noted that patients with alcoholic non-cirrhotic liver disease have an increased risk of hepatotoxic effects from paracetamol in cases of overdose. The product may affect laboratory test results for blood glucose and uric acid levels.

Patients who take analgesics daily for mild forms of arthritis should consult their physician.

Keep the medicinal product out of sight and reach of children.

Excipients

This medicinal product contains sodium in the amount of 415 mg per tablet. Caution is advised when administering to patients on a sodium-restricted diet.

This medicinal product contains sorbitol. If a patient has been diagnosed with intolerance to certain sugars, medical advice should be sought before taking this medicinal product.

This medicinal product contains aspartame, a phenylalanine derivative, which may be harmful for patients with phenylketonuria (see section "Contraindications").

Use during pregnancy or breastfeeding

Use during pregnancy is not recommended, as there is an increased risk of spontaneous abortion associated with caffeine use.

Use of this medicinal product is not recommended in women who are breastfeeding. Paracetamol and caffeine pass into breast milk. Caffeine may have a stimulant effect on breastfed infants, although significant toxicity has not been observed.

Ability to influence reaction speed when driving or operating machinery. The likelihood of effect is very low.

Method of Administration and Dosage

The medicinal product is intended for oral administration. The required number of effervescent tablets should be dissolved in half a glass of water and taken orally.

Do not exceed the recommended dose.

The lowest effective dose required to achieve the therapeutic effect should be used for the shortest possible duration. The interval between doses should be at least 4 hours. Do not use for more than 3 days without consulting a physician.

Adults, elderly patients, and children aged 16 years and older

1–2 tablets every 4–6 hours as needed (up to 4 times daily). Do not take more than 8 tablets (4000 mg paracetamol / 520 mg caffeine) within 24 hours.

Children aged 12 to 15 years

1 tablet every 4–6 hours as needed (up to 4 times daily). Do not take more than 4 tablets (2000 mg paracetamol / 260 mg caffeine) within 24 hours.

Children. The use of this medication is not recommended in children under 12 years of age.

Overdose

Paracetamol

Paracetamol overdose may cause liver failure, which could lead to the need for liver transplantation or result in death. Acute pancreatitis has been observed, usually in conjunction with liver function abnormalities and hepatotoxicity. Liver damage may occur in adults who have ingested 6–8 g or more of paracetamol, and in children who have ingested more than 150 mg/kg body weight. In patients with risk factors [long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John’s wort, or other drugs inducing liver enzymes; chronic excessive alcohol consumption; glutathione depletion (e.g., malnutrition, cystic fibrosis, HIV infection, fasting, cachexia)], ingestion of 5 g or more of paracetamol may lead to liver damage.

In case of overdose, immediate medical attention is required. Treatment should be initiated promptly. The patient should be taken to a hospital even if no early symptoms of overdose are present.

Symptoms within the first 24 hours: pallor, nausea, vomiting, loss of appetite, and abdominal pain. Clinical experience shows that signs of liver damage typically become apparent 24–48 hours after overdose and usually peak within 4–6 days. Glucose metabolism disorders and metabolic acidosis may occur.

Symptoms of overdose may not reflect the severity of overdose or the risk of organ damage. Immediate medical intervention is necessary even in the absence of symptoms. If overdose is confirmed or suspected, the patient must be taken to the nearest medical facility capable of providing emergency care and appropriate treatment. This is essential even if no symptoms are present, due to the risk of delayed liver damage. Activated charcoal should be considered if administered within 1 hour of paracetamol ingestion. Plasma paracetamol concentration should be measured at least 4 hours after ingestion (earlier measurements are unreliable). Treatment with N-acetylcysteine may be administered within 24 hours of paracetamol ingestion, but maximum protective effect is achieved when administered within 8 hours of overdose. The efficacy of the antidote decreases significantly after this time. If required, intravenous N-acetylcysteine should be administered according to the recommended dosing regimen. In the absence of vomiting, oral methionine may be used as an alternative, particularly in remote areas outside hospital settings.

In severe poisoning, liver failure may progress to encephalopathy, hemorrhage, hypoglycemia, coma, and may be fatal. Acute renal failure with acute tubular necrosis may present with severe flank pain, hematuria, proteinuria, and may develop even in the absence of severe liver damage. Cardiac arrhythmias have also been reported.

With prolonged use of the drug in high doses, hematological disorders such as aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia may develop. High-dose intake may affect the central nervous system, causing dizziness, psychomotor excitation, and disorientation. In the urinary system, nephrotoxicity may occur (renal colic, interstitial nephritis, capillary necrosis).

Caffeine

Caffeine overdose may cause epigastric pain, vomiting, diuresis, rapid breathing, tachycardia or cardiac arrhythmia, and affect the central nervous system (insomnia, restlessness, nervous excitation, anxiety, agitation, dizziness, irritability, affective disturbances, tremor, seizures). Clinically significant symptoms of caffeine overdose may also be associated with severe liver damage caused by paracetamol, which may occur after ingestion of a dose sufficient to cause caffeine overdose. There is no specific antidote, but supportive measures such as beta-adrenergic antagonists may help alleviate cardiotoxic effects. Gastric lavage is recommended; oxygen therapy is advised, and diazepam may be administered in case of seizures. Symptomatic therapy is required.

Sodium bicarbonate

High doses of sodium bicarbonate may cause gastrointestinal disturbances such as belching and nausea, and may also lead to hypernatremia; therefore, electrolyte balance should be monitored and appropriate treatment provided to patients.

Adverse Reactions

The frequency of the adverse reactions listed below is unknown; however, they are most likely rare (< 1/10,000).

Adverse reactions associated with paracetamol

Blood and lymphatic system disorders: thrombocytopenia, agranulocytosis.

Immune system disorders: anaphylaxis, skin hypersensitivity reactions including rash, angioneurotic edema, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Respiratory, thoracic and mediastinal disorders: bronchospasm in patients sensitive to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs.

Hepatobiliary disorders: liver function abnormalities.

Metabolism and nutrition disorders: metabolic acidosis with high anion gap.

Adverse reactions associated with caffeine

Central nervous system disorders: dizziness, headache.

Cardiac disorders: tachycardia.

Gastrointestinal disorders: gastrointestinal discomfort.

Psychiatric disorders: insomnia, restlessness, anxiety, irritability, nervousness.

Concomitant use of this medicinal product at recommended doses with products containing caffeine may result in increased caffeine intake, which can intensify caffeine-related adverse effects such as insomnia, restlessness, anxiety, irritability, headache, gastrointestinal disturbances, and tachycardia.

Description of selected adverse reactions

Metabolic acidosis with high anion gap

Cases of metabolic acidosis with high anion gap due to pyroglutamic acidosis have been observed in patients with risk factors who were treated with paracetamol (see section "Special precautions for use"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report any suspected adverse reactions and lack of therapeutic effect via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions. Store at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging. 4 tablets in a strip; 3 strips in a cardboard pack.

Authorization category. Over-the-counter (without prescription).

Manufacturer. KUSUM HEALTHCARE PVT LTD /
KUSUM HEALTHCARE PVT LTD.

Manufacturer's address and location of operations
Plot No. M-3, Indore Special Economic Zone, Phase-II, Pithampur, Distt. Dhar, Madhya Pradesh, Pin 454774, India /
Plot No. M-3, Indore Special Economic Zone, Phase-II, Pithampur, Distt. Dhar, Madhya Pradesh, Pin 454774, India